Efficacy and safety of Changsulin ? compared with Lantus ? in type 2 diabetes: a phase Ⅲ multicenter, randomized, open-label, parallel, controlled clinical trial / 中华内科杂志

Objective:To compare the efficacy and safety of Changsulin ? with Lantus ? in treating patients with type 2 diabetes mellitus (T2DM). Methods:This was a phase Ⅲ, multicenter, randomized, open-label, parallel-group, active-controlled clinical trial. A total of 578 participants with T2DM inadequately controlled on oral hypoglycemic agents were randomized 3∶1 to Changsulin ? or Lantus ? treatment for 24 weeks. The efficacy measures included changes in glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), 2h postprandial plasma glucose (2hPG), 8-point self-monitoring of blood glucose (SMBG) profiles from baseline, and proportions of subjects achieving targets of HbA1c and FPG. The safety outcomes included rates of hypoglycemia, adverse events (AEs) and anti-insulin glargine antibody. Results:After 24 weeks of treatment, mean HbAlc decreased 1.16% and 1.25%, FPG decreased 3.05 mmol/L and 2.90 mmol/L, 2hPG decreased 2.49 mmol/L and 2.38 mmol/L in Changsulin ? and in Lantus ?, respectively. No significant differences could be viewed in above parameters between the two groups (all P>0.05). There were also no significant differences between Changsulin ? and Lantus ? in 8-point SMBG profiles from baseline and proportions of subjects achieving the targets of HbA1c and FPG (all P>0.05). The rates of total hypoglycemia (38.00% and 39.01% for Changsulin ? and Lantus ?, respectively) and nocturnal hypoglycemia (17.25% and 16.31% for Changsulin ? and Lantus ?, respectively) were similar between the two groups (all P>0.05). Most of the hypoglycemia events were asymptomatic, and no severe hypoglycemia were found in both groups. No differences were observed in rates of AEs (61.77% vs.52.48%) and anti-insulin glargine antibody (after 24 weeks of treatment, 6.91% vs.3.65%) between the two groups (all P>0.05). Conclusions:Changsulin ? shows similar efficacy and safety profiles compared with Lantus ? and Changsulin ? treatment was well tolerated in patients with T2DM.

Clinical value of sulfornylureas in type 2 diabetes management in China / 中华内分泌代谢杂志

The clinical practice of diabetes management is facing challenge in China,old anti-diabetic drugs such as sulfonylureas have been used for more than 60 years, and they are still valuable in diabetes management because of their remarkable hypoglycemic effect,as well as good safety,clear adverse events and cost-effectiveness.

Efficacy and safety of sodium glucose co-transporter 2 inhibitors(SGLT2i) in the treatment of type 2 diabetes / 中华内分泌代谢杂志

[Summary] As of 2014, an estimated 387 million people have diabetes mellitus ( DM) worldwide, which represents 8.3%of the adult population.China Noncommunicable Disease Surveillance in 2010 shows that the overall prevalence of DM is estimated to be 11.6%(approximately 113.9 million) in the Chinese adult population, with the prevalence among men of 12.1%and women of 11.0%, respectively.Control of blood glucose is fundamental to DM management.Despite the availability of several antihyperglycemic agents, only 53%of patients with DM achieve the recommended goals for DM care of HbA1C<7.0%.According to the National Health and Nutrition Examination Survey and the Behavioral Risk Factor Surveillance System Survey during the period of 10 years in the United States, 33.4%to 48.7%of persons with DM still have not met the targets for glycemic control, blood pressure or lipid level.In order to improve glycemic control, there is a need for new therapeutic options with innovative mechanisms of action and acceptable safety profiles.As a newly developed class of oral antidiabetic drugs, sodium-glucose co-transporter 2 inhibitors(SGLT2i) have recently been approved for the treatment of patients with type 2 diabetes mellitus, including canagliflozin, dapagliflozin, and empagliflozin.Evidence from clinical trials has suggested promising efficacy and safety of SGLT2i when used as monotherapy or in combination with other antihyperglycemic medications.SGLT2i significantly reduce HbA1C and fasting plasma glucose, and are well tolerated in general with a low intrinsic propensity to cause hypoglycemia, as well as rare severe renal or cardiovascular adverse events reported.

Gut hormones in obesity and diabetes / 中国糖尿病杂志

[Summary] Pathophysiological mechanisms of obesity and type 2 diabetes is complex . In recent years ,data has showed that guthormone in obesity and T 2DM patients has changed ,and guthormones such as GLP-1 ,GIP ,PYY ,CCK and ghrelin are strongly related to the development of obesity and diabetes , resulting in a series of metabolic disorders ,this may be one of causes of the development of obesity and T2DM. In recent years ,the guthormone-based treatments or therapies associated with guthormone have became one of the hot topics in the diabetes research. Currently ,some guthormone-based treatment shave been used in clinical treatment of diabetes. This paper is a literature review on the history of gut hormones ,and how it affect the development of diabetes and obesity ,as well as aspects of clinical practice.

Effectiveness and safety of initiation of once-daily insulin detemir in Chinese patients with type 2 diabetes previously treated with different quantifies of oral anti-diabetic drugs: subgroup analysis of the Chinese SOLVETM Study / 中华内科杂志

Objective To evaluate the effectiveness and safety on once-daily (OD) insulin detemir (IDet) in Chinese patients with type 2 diabetes mellitus (T2DM) who were treated with different types or combinations of oral anti-diabetic drugs (OADs).Methods The SOLVETM study was a 24-week observational study on the initiation of IDet OD in T2DM patients with uncontrolled hyperglycemia on diet,exercise,and one or more OADs.Subjects were grouped based on the numbers of OADs taken before (＞ 2-OAD,2-OAD,and 1-OAD groups).Efficacy and safety endpoints were evaluated and compared in different groups.Results This study includes 3 272 patients,among them 464 (14.2％) were treated with more than 2OADs,1511 (46.2％) with 2OADs,and 1 218 (37.2％) with 1OAD before the study.The mean glycosylated hemoglobin A1c (HbA1c) was 8.4％,8.3％,8.4％ at baseline,and 7.3％,7.2％,7.1％ at the end of 24-week in each 3 groups (all P ＜0.001 vs.baseline values).The HbA1c reductions were not statistically significant different among groups.Body weight tended to decrease in patients from all groups,however,only that in the 2-OAD group reached statistically significance.No major hypoglycaemia events were reported.However,the overall minor hypoglycaemia rate in the 2-OAD group was higher at the end of the study than that at baseline (P ＜ 0.05).No differences in the rate of nocturnal minor hypoglycaemia were observed in all groups after IDet treatment.Conclusion Initiation of IDet OD was effective and well-tolerated in Chinese patients with T2DM whose glycemia was poorly controlled on OADs irrespective of the number of OADs taken before.(registration number NCT00825643)

Biphasic insulin aspart 30 improved glycemic control in Chinese patients with type 2 diabetes poorly controlled on oral glucose-lowering drugs: a subgroup analysis of the A₁chieve study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The effectiveness and safety of initiating biphasic insulin aspart 30 in patients who were poorly controlled on oral glucose-lowering drugs were studied in randomized controlled trials, while results from clinical practice remain limited. This subgroup analysis was to provide such findings from a large-scale non-interventional study.</p><p><b>METHODS</b>A1chieve was a multinational, prospective, open-label, non-interventional, 24-week study in patients with type 2 diabetes initiating insulin analogues in 28 countries across Asia, Africa, Europe, and Latin America. After physician had taken the decision to use this insulin, any patient with type 2 diabetes who was not treated with or who had started the study insulin within 4 weeks before inclusion was eligible. Patients were treated with study insulin alone or in combination with oral glucose-lowering drugs. Data on adverse drug reactions, hypoglycemia and glycemic control were collected at baseline, week 12 and 24. This is a report of a Chinese subgroup analysis from the A1chieve study.</p><p><b>RESULTS</b>Totally, 4 100 patients constituted this subgroup. No serious adverse drug reactions were reported. Rates of total, major, nocturnal hypoglycemic events (events/patient per year) were 1.47, 0.10, 0.31 at baseline and 1.35, 0.00, 0.22 at week 24, respectively. Glycemic control was improved as measured by hemoglobin A1c (mean 9.3% to 7.0%, reduction -2.3%), fasting plasma glucose (mean 10.2 to 6.8 mmol/L, reduction -3.5 mmol/L) and postprandial plasma glucose (mean 14.4 to 8.8 mmol/L, reduction -5.6 mmol/L), all P < 0.001. Change in mean body weight was +0.3 kg (P < 0.001).</p><p><b>CONCLUSION</b>In this subgroup analysis of the A1chieve study, biphasic insulin aspart 30 improved glycemic control with low risk of hypoglycemia.</p>

Role of cardiovascular protection played by dipeptidyl peptidase 4 inhibitors / 中华内分泌代谢杂志

Cardiovascular disease is a common complication of type 2 diabetes,causing considerable fatality.Dipeptidyl peptidase 4 (DPP-4) inhibitors are new drugs for treatment of diabetes.Current studies have demonstrated that these drugs play an important role in cardiovascular protection.DPP-4 inhibitors can lower blood pressure,regulate blood lipid,and suppress inflammation and atherosclerosis.Treatment with DPP-4 inhibitors results in reduced size of myocardial infarct,reduced myocardial ischemia/reperfusion injury,increased myocardial cell regeneration,and improved heart function,etc.Recent studies have also found that DPP-4 inhibitors are able to mobilize progenitor cells to the sites of cardiovascular injury and thus to promote tissue repair.

Mechanism of insulin resistance of islet beta-cells in rat after long term lipid infusion / 中国医师杂志

Objective To study the changes and mechanism of the function of islet βcells and insulin signal transduction molecules in rats after long-term period lipid infusion.Methods Thirty SpragueDawley (SD) rats were randomly divided into free fatty acid (FFA) and normal saline (NS) groups.Catheters were implanted under pentobarbital anesthesia in the right atrium via the jugular vein and the left carotid artery.A technique for a 72-h infusion in unrestrained rats was used for triglyceride and heparin or saline infusion.The infusion period was started on day 2 after surgery.After 72-h infusion,fasting serum insulin (Ins) and FFA in the blood were determined.The glucose infusion rat (GIR) was measured by hyperinsulinemia euglycemic clamp to evaluate the peripheral insulin resistance.The intravenous glucose tolerance test (ivgtt) and islet cell perifusion was conducted to evaluate the function of islet β-cell.The rats in two groups were sacrificed,and the pancreatic islets were isolated and collected.The levels of malondialdehyde (MDA) and reduced glutathione hormone (GSH) were detected in pancreatic tissues.The expressions of insulin receptor substrate-1 (IRS-1),insulin receptor substrate-2 (IRS-2),and glucose transporter-2 (Glut2)gene in islets were detected by real-time polymerase chain reaction (PCR).Results (1)The serum FFA concentration in the FFA group was higher than in NS group [(1.56 ± 0.21) mmol/L vs (0.65 ± 0.12)mmol/L,P ＜0.01].(2)The GIR was decreased significantly in FFA group compared with NS group(P ＜0.01).(3)The glucose that stimulated insulin secretion was decreased in the FFA group.(4)The levels of MDA were significantly higher in FFA group [(1.62 ± O.18) mmol/mg prot vs (0.76 ± 0.15) mmol/mg prot,P ＜0.01].The levels of GSH were lower in FFA group [(22.54 ±2.66) mg/g prot vs (36.58 ± 3.02) mg/g prot,P ＜ 0.01].(5) The gene cxprcssion of IRS-1 in islets was significantly decreased by [(36.8±1.8)％,P ＜0.01],and the expression of IRS-2 and Glut-2 was decreased by [(29.6±1.2) ％] and [(58.7 ± 2.1) ％] in FFA group,respectively(all P ＜0.01).Conclusions Lipid infusion in long time decreased the secretion of insulin and impaired the expression of insulin signal transduction molecules in islet βcells.

The baseline characteristics of patients with type 2 diabetes initiating insulin detemir:the Chinese cohort from the SOLVETM study / 中华内科杂志

Objective To characterize the baseline status of Chinese diabetic patients based on data derived from Chinese cohort from SOLVETM study.Methods Patients with type 2 diabetes initiating basal insulin detemir at the decision of the physician were eligible for the study.Data on demographics,medical history,glycemic profile and treatment regimen at baseline were collected by physicians.Results A total of 3272 patients [female 42％,male 58％,mean age (56.2 ± 10.8) years] were included in the study.Their BMI was (25.3 ± 3.3) kg/m2.The duration of diabetes was 4.0 (0.1-27.0) years,and the duration of treatment with oral antidiabetic drugs (OADs) was 3.0(0.0-20.2) years.The proportions of subjects with diabetic macro-and micro-vascular complications were 15.8％ (515 cases) and 27.1％ (866 cases),respectively.The hemoglobin Al c (HbAl c) at baseline was (8.33 ± 1.70) ％,and the fasting blood glucose (FPG) was (9.5 ± 2.6) mmol/L.Conclusions A large proportion of patients with type 2 diabetes remain in poor glycemic control,and the prevalence of diabetic complications is high,which requires optimal therapeutic strategy for the patients with suboptimal glycemic control.

The protection of islet β-cells in db/db mice by combination pioglitazone and glucagon like peptide-1 treatment / 中华内科杂志

ObjectivesTo evaluate the effect of combination of liraglutide,a glucagon-like peptide-1 analogue and pioglitazone,an insulin sensitizer,on diabetic db/db mice.MethodsThirty-five 8-week old male db/db mice were divided into control group (n = 8 ),pioglitazone group (n =9 ),liraglutide group (n =9) and combined therapeutic group (n =9),which was given normal saline 0.1 ml,2/d,pioglitazone 24 mg· kg-1 · d-1 (feed contained 0.02％ pioglitazone) + normal saline 0.1 ml,2/d,liraglutide 300 mg/kg,2/d,and pioglitazone 20 mg · kg-1 · d -1 ( feed contained 0.02％ pioglitazone) +liraglutide 300 mg/kg,2/d,respectively.Liraglutide were given at 8:00 and 16:00 via subcutaneous injection after having been diluted with sterilized normal saline.Effect on glucose,lipid metabolism and islet β-cell preservation were assessed after 4 weeks.Oneway ANOVA was adopted for statistical analysis.Results Combination therapy displayed promising anti-hyperglycemic[glycosylated hemoglobin Alc: (4.5 ± 0.6)％vs.(7.3 ±0.4)％,P ＜ 0.001].Glucose tolerance were improved assessed by area under curve(AUC) of glucose by intraperitoneal glucose tolerance test (IPGTT)[(1814 ±91 ) mmol · min · L-1 vs.(4042 ±183) mmol · min · L-1,P ＜0.001];insulin release response to glucose were also preserved as AUC of insulin by IPGTT was higher[( 1639 ±372) μg · min · L-1 vs.(834 ±201 )μg · min · L-1].Combination therapy also reduced circulated free fatty acids and TG[( 202.0 ± 20.4 ) μmol/L vs.( 272.5 ± 21.7 )μmol/L,(0.81 ± 0.28) mmol/L vs.( 1.35 ± 0.21 ) mmol/L],and increased plasma adiponectin [(16.7±2.0)mg/L vs.(10.2±1.8)mg/L].All P value ＜0.05.Islet immunohistochemistry showed that combination therapy significantly increased insulin positive area were[( 59.5 ± 1.5 ) ％ vs.( 22.4 ±1.5) ％]and ratio of Brdu positive β-cells was three folds than vehicle-treated mice[( 2.4 ± 0.5 ) ％ vs.(0.8 ±0.3)％],both greater than each single treatment.Combined therapy significantly improved islet β cell/α cell distribution,which led to islet recovery.ConclusionsCombined therapy improves glucose and lipid metabolism,preserves islet β-cell function and stimulates β-cell proliferation,greater than either liraglutide or pioglitazone treatment alone.

The latest research progress of human GLP-1 analogues liraglutide / 中华内分泌代谢杂志

The novel drug class of Glucagon-like peptide-1 ( GLP-1 ) analogue is extremely promising,since they can address many of the unmet needs of diabetes treatment. This article summarized physiological action of GLP-1 and delayed mechanisms of long-acting human GLP-1 analogue liraglutide. Simultaneously, the latest basic and clinical research results of liraglutide were reported especially.

Improving glucose intolerance linked with the reduction of cardiovascular disease events and mortality in a Da Qing population with pre-diabetes-a 20 year follow-up study / 中华内分泌代谢杂志

Objective To investigate if improving or slowing the progression of glucose intolerance might be linked with the reduction of cardiovascular disease(CVD)events and mortality in a Da Qing population with prediabetes.Methods In 1986,577 subjects with impaired glucose tolerance in 33 clinics in Daqing city were randomly assigned to either the control group or one of three lifestyle intervention groups(diet,exercise,or diet plus exercise)to receive a 6 year lifestyle intervention.All the participants were followed for 14 years(1993-2006)after completion of the 6 year active interventions to assess the long-term effect of the interventions.In this post-hoc analysis,the participants were stratified into four subgroups(quartiles)based on their 2 h plasma glucose(2hPG)level after glucose loading at the end of the active intervention,in order to analyze the impact of plasma glucose level on CVD events and mortality.Results During the 20-year follow-up,there were a total of 142 deaths(68 of which were attributed to CVD)and 211 first CVD events(145 strokes and 66 myocardial infarctions).From the highest to the lowest levels of 2hPG in the 4 quartiles,the all-cause mortality(17.8,12.7,10.9,and 9.7/1 000 personyears),CVD mortality(9.1,5.9,6.1,and 4.9/1 1300 person-years)and the incidence of first CVD events(30.4.24.0,18.8,and 19.7/1 000 person-years)showed a clear trend of decline.In multivariate analyses,controlled for age,sex,body mass index,smoking habit,blood pressure,and intervention methods at baseline,the results showed that the 5 mmol/L elevation of 2hPG level after glucose loading in 1992 significantly increased the all-cause mortality(HR 1.335.P=0.005),the incidences offirst CVD events(HR 1.227,P=0.012)and stroke(HR 1.213,P=0.026).Conclusion In pre-diabetes population.if the lifestyle intenrentions are substantially efficacious in improving glucose intolerance,the CVD risk and mortality will be reduced.

Role of pancreatic stellate cell activation in islet fibrosis of rats fed with high-fat / 中华内分泌代谢杂志

Pancreatic stellate cell (PSC) activation in islet fibrosis of insulin-resistant rats induced by high-fat diet was investigated. After 20 weeks, the glucose infusion rate and glucose-stimulated insulin secretion in high-fat group were significantly decreased while fasting plasma glucose, fasting serum insulin, free fatty acid and the basal glucagon secretion were significantly increased compared with those parameters of the control rats (P< 0.05 or P<0.01). Activated PSC and collagen fiber ( type Ⅰ and Ⅲ) were found in islets of rats fed with high-fat. The result suggests that PSC activation, proliferation and migration to islet may contribute to islet fibrosis in insulin-resistant rats.

A multi-center clinical study of the reference value of serum glycated albumin / 中华内科杂志

Objective To set up the reference value of serum glyeated albumin (CA) in Chinese for using in clinical practice through a multi-center clinical trial. Methods Three hundred and eighty individuals with normal weight and normal glucose regulation, including 183 males and 197 females ranging from 20 to 69 years, were recruited from 10 hospitals in China. Serum GA levels were measured with liquid enzymatic method. Results (1) The GA level of the 380 subjects was (14. 5±1.9)%. When dividing these subjects by age into 3 subgroups, there was no difference in the GA levels among the 3 subgroups (P>0.05). Compared with the women, the men had higher GA level in the first subgroup aging from 20 to 39 (P =0.028). However, no significant difference was detected after adjusting with BMI as confounder.(2) When dividing those subjects by BMI into 3 subgroups, with BMI ranging from 18. 5-20. 9 kg/m2,21.0-22. 9 kg/m<'2>and 23.0-24. 9 kg/m<'2>respectively, we came to the following results: for men, there was no difference in the GA levels among the 3 subgroups (P>0.05), but for women, the GA level of the first subgroup was higher than that of the second subgroup (P =0.024). (3) The level of GA in the 2. 5th to 97.5th percentile was 10. 8%-17. 1%. (4) Sixty normal subjects were chosen to repeat evaluation of GA levels after 2-3 weeks and the GA levels were of no difference (P>0.05).Conclusion The normal range of serum GA for the Chinese population could be suggested at 11%-17%.

Preservation of β-cell function in type 2 diabetes by GLP-1 based therapy / 中华内分泌代谢杂志

Type 2 diabetes is characterized by deteriorated β-cell function and progressive loss of β-cell mass. Pancreatic islets are a target of high concentrations of glucose, pro-inflammatory cytokines and free fatty acid levels, which are associated with obesity, insulin resistance and β-cell apeptosis. Therapy targeting β-cell dysfunction is crucial in the treatment of type 2 diabetes. GLP-1, one of the incretin hormones, has been demonstrated to improve glycaemic control and β-cell function through its multiple physiological effects. In this review, the mechanisms involved in β-cell dysfunction and β-cell loss are addressed, and the updates in GLP-1 based therapy for the preservation of β-cell mass and β-cell function in type 2 diabetes are also reviewed.

Prevention-based control and standardized management——China Guideline for Type 2 Diabetes (2007 Edition) / 中华内分泌代谢杂志

The patients of type 2 diabetes mellitus are increasing, which has become one of the most daunting causes of sickness and death in China. "China Guideline for Type 2 Diabetes"(2007 Edition) is prepared by the Chinese Diabetes Society on the basis of new evidence related to prevention of both diabetes and its complications, the update guidelines of many international organizations, as well as the clinical practice in China. The diagnostic criteria for dysglycemia in China are pointed out. The importance of not only diabetes prevention and management but also multifactorial intervention of cardiovascular risk factors is emphasized. More strict targets of glycemic control are recommended, however, the strategy of glycemic control should be based on pathophysiological features of Chinese diabetic population. The new guideline delivers the idea of "prevention-based control and standardized management". The guideline training program will foster the qualified health care providers and improve the process of diabetes care.

Diabetes associated cognitive impairment: a problem should not be ignored / 中华内分泌代谢杂志

Diabetes can affect structure and function of brain in several aspects, but diabetic cognitive impairment is often ignored. The pathogenesis of diabetes associated cognitive impairment is complicated. Factors such as glucotoxicity, lipotoxicity, insulin resistance, hypoglycaemia and disturbance of Ca2 homeostasis may play important roles. Besides conventional diabetes therapy, new methods still need to be explored.

Determination of Aluminum in Drinking Water by Graphite Furnace Atomic Absorption Spectrometry / 环境与健康杂志

Objective To establish a method for determination of aluminum in water by graphite furnace atomic absorption spectrometry (GFAAS). Methods Aluminum in water was directly determined by GFAAS at wavelength of 394.4 nm without any matrix modifiers. Results A good linearity (r=0.999 5) was obtained, the linear range was 0-0.600 mg/L. RSD of samples ranged from 2.1% to 6.4%, the average rates of recovery were between 91.0%-108.0%. The detection limit of the method was 0.6 ?g/L, the quantitative limit was 1.9 ?g/L. There was no significant difference between the results determined at wavelength of 394.4 nm and 309.3 nm. Conclusion This method is simple, rapid, accurate and has a wide linear range. It can be applied in the determination of aluminum in drinking water.